Publications from N.Osborne

• Andrade da Costa Belmira LdS, Kang Kui D, Rittenhouse Kay D, and Osborne Neville N (2009) The localization of PGE2 receptor subtypes in rat retinal cultures and the neuroprotective effect of the EP2 agonist butaprost. Neurochem Int, 55(4):199-207.

• Osborne Neville N (2009) Recent clinical findings with memantine should not mean that the idea of neuroprotection in glaucoma is abandoned. Acta Ophthalmol, 87(4):450-4.

• Osborne Neville N, Li Guang-Yu, Ji Dan, Andrade da Costa Belmira L, Fawcett Rebecca J, Kang Kui D, and Rittenhouse Kay D (2009) Expression of prostaglandin PGE2 receptors under conditions of aging and stress and the protective effect of the EP2 agonist butaprost on retinal ischemia. Invest Ophthalmol Vis Sci, 50(7):3238-48.

• Chidlow Glyn, Wood John PM, Manavis Jim, Osborne Neville N, and Casson Robert J (2008) Expression of osteopontin in the rat retina: effects of excitotoxic and ischemic injuries. Invest Ophthalmol Vis Sci, 49(2):762-71.

• Costa Belmira LdSAd, Fawcett Rebecca, Li Guang-Yu, Safa Rukhsana, and Osborne Neville N (2008) Orally administered epigallocatechin gallate attenuates light-induced photoreceptor damage. Brain Res Bull, 76(4):412-23.

In 1979 my research changed from working on single snail neurones to an analysis of cells in the retina. Whereas I initially isolated retinal cell groups (ganglion cells) for biochemical analysis, I then began to use another approach, that of localising the different cell-types by the specific antigens. I not only made a number of antibodies to neuropeptides (substance P, neuropeptide Y) but used antibodies from different sources to demonstrate that localisation of certain neurotransmitters is associated with specific neurone-types both in the intact retina and in retinal cultures. This enabled us to carry out a variety of experiements which had previously been impossible. We were the first to describe the cell-types in the retina containing serotonin, tyrosine-hydroxylase, substance P, neuropeptide Y and cholecystokinin, for example.

Serotonin as a neurotransmitter in the retina: One of my main research aims in the 1980s was to prove that serotonin has a functional role in the retina. This was partly because it was stated in the literature that serotonin does not have such a role in the retina and partly because I had a general interest in serotonin as a mediator. Through a series of experiments which involved use of immunocytochemistry, pharmacology, biochemistry, physiology and most recently molecular biology it was demonstrated that serotonin acts as a transmitter / mediator in retinas from both mammalian and non-mammalian species. Our most recent result is to show by in situ hybridisation studies that 5-HT7-type receptors are associated with the ganglion cells and that these receptors are affected by ischaemia.

Signal transduction in ocular tissues: Another major area of research over the past six years has been the analysis of the transduction processes associated with specific receptors in the iris, ciliary body, retina and retinal pigment epithelium. We have produced extensive data on these subjects, concentrating particularly on receptors related to the activation of phosphoinositides and cAMP and the involvement of calcium and protein kinase C. In our most recent studies we have demonstrated the existence of melatonin receptors in the retinal pigment epithelium cells and iris.ciliary body and studies are now being conducted to elucidate their functional roles in relation to phagocytosis and the control of intraocular pressure.

Interactions between the outer retina and the pigment epithelium: Besides studying the neurobiology of the retina extensively I am also interested in understanding the interaction of the photoreceptors with the retinal pigment epithelium. The breakdown of the normal homeostasis of these two cells has been implicated in the loss of the visual cells associated with Retinitis Pigmentosa and Age-Related Macular Degeneration. The aim of this work is to suggest types of drugs that could be used to delay the onset of photoreceptor cell death and hence provide some treatment for these diseases.

Control of Intraocular Pressure: I am also interested in the factors that control the secretion of aqueous fluid and thus influence the intraocular pressure (IOP). The drugs used to reduce IOP are currently employed to treat glaucoma and the aim of these studies is to identify other drugs which maybe suitable for clinical use, especially those that might also possess neuroprotective properties (see below). I am currently particularly interested in developing drugs which could affect the influence on IOP by serotonin and melatonin receptors.

Retinal ischaemia and glaucoma: Within the last three years I have directed a significant part of my research at studies on retinal ischaemia. In glaucoma it is clear that lowering intraocular pressure itself does not prevent the loss of patients' vision. It is probable that the retina suffers because of ischaemia and it will therefore be necessary to develop procedures to arrest these ischaemia-induced insults to treat this disorder effectively. Moreover, ischaemia is also known to play a role in the damaging effects on the retina of diseases such as diabetes. We have therefore developed several experimental models to mimic these forms of ischaemia and these have been characterised to identify what happens to the retina during such insults. We have also shown that certain drugs which are already used by man can arrest the ischaemic-induced insults to the retina. Of particular interest is our observation that betaxolol, a known b -antagonist currently used to lower intraocular pressure in glaucoma, is also a neuroprotective agent. Thus betaxolol, in contrast to other substances known to reduce only intraocular pressure, will have an advantage for treatment of glaucoma. The implications of our findings are obvious.

Other Activities

Governing Body Fellow at Green College,
Lecturer in Biochemical Pharmacology at Christ Church College

• Alcon Prize Award (1986)
• Merit Shield Award from University of Venezuela (1987)
• Paul Kayser Award (1990)
• Distinguished Lecture Award from NewOrleans University (1997)
• 2nd Jessie Mole Prize Lecture (2002)
• Edre A. Balazs Prize (2004)

Editorial Boards

• Progress in Retinal and Eye Research (Co-editor)
• Ophthalmic Research (Editorial Board)
• Graaefe's Arch Clin Exp Ophthalmol (Editorial Board)

Professional Membership

• International Society of Neurochemistry (ISN)
• The Biochemical Society
• British Pharmaacological Society
• International Society of Eye Research (ISER)
• Association of Vision and Eye Research (ARVO)
• European Vision and Eye Research (EVER)

Committees

• Fellowship and General Committees (Green College)
• European Representative on ICER
• External M.Sc. examiner in Neurosciences (Roehampton College / Surrey University)